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Nat Genet2026;58(2):355-365.February 1, 2026Journal Article

Genomic evolution of pancreatic cancer at single-cell resolution.

Haochen Zhang1,2,3, Palash Sashittal4,5, Elias-Ramzey Karnoub2,6,7, Akhil Jakatdar4, Shigeaki Umeda2,6, Jungeui Hong2,6, Anne Marie Noronha8, Agustin Cardenas6, Amanda Erakky6, Caitlin A McIntyre9, Akimasa Hayashi6,10, Nicolas Lecomte2,6, Marc Hilmi6,11, Wungki Park6,12,13, Nan Pang14, Eileen M O'Reilly6,12,13, Alice C Wei6,13,14, Benjamin J Raphael15, Christine A Iacobuzio-Donahue16,17,18
1Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
2Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
3Valar Labs, Palo Alto, CA, USA.
4Department of Computer Science, Princeton University, Princeton, NJ, USA.
5Department of Computer Science, Virginia Tech, Blacksburg, VA, USA.
6David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
7Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
8Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
9Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
10Department of Pathology, Kyorin University, Mitaka-shi, Tokyo, Japan.
11Institut Curie, Paris, France.
12Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
13Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.
14Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
15Department of Computer Science, Princeton University, Princeton, NJ, USA. braphael@princeton.edu.
16Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA. iacobuzc@mskcc.org.
17David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York City, NY, USA. iacobuzc@mskcc.org.
18Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA. iacobuzc@mskcc.org.
PubMed PMC DOI PDF

Abstract

Most evolutionary studies on pancreatic cancer rely on bulk sequencing, yet clonal evolution happens at the single-cell level. We used single-nucleus DNA sequencing to study 137,491 single nuclei from 24 pancreatic neoplasms reflecting various clinical scenarios. We found higher frequencies of somatic alterations to driver genes that bulk studies indicate; many manifest as copy number alterations…

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